Male infertility has been on the rise for several decades and is now considered a major health problem affecting around one in twelve of the men in USA. Id. If the trends observed over the last century continues, some infertility experts predict that by the middle of this century, most men will be advised to freeze their sperm at a young age to ensure adequate sperm quality.
A successful fertilization and subsequent embryo development requires properly matured sperm chromatin with minimal damage to its DNA integrity. Equally important, is the integrity of sperm membrane lipid structure essential for sperm motility and sperm-oocyte fusion. At least one of the causes of sperm DNA damage and membrane peroxidation is attributed to excess Reactive Molecular Species (“RMS”), most importantly Reactive Oxygen Species (“ROS”), leading to a condition commonly referred to as sperm oxidative stress. In general, the term “Oxidative Stress” refers to a condition that occurs as a result of excessive generation of ROS and/or a diminished capacity of ROS scavenging endogenous antioxidants. Accordingly, the excess concentration of ROS overwhelms the local environmental antioxidant defense mechanism of the spermatozoa potentially leading to the formation of sperm cells with lower or no fertilizing potential.
Under normal conditions, cells utilize an array of enzymatic and non-enzymatic antioxidants as internal defense to scavenge and neutralize excess levels of ROS. It is believed that oxidative stress develops either because of an overabundance of ROS from environmental or pathological stressors or a lack of antioxidant capacity to neutralize excess concentrations of ROS. Excess ROS within semen and the sperm cell has been described to cause degradation of the cellular components such as membrane and DNA, hence, the sperms injured by such oxidative species have diminished or no fertility potential.
To date several studies have reported that levels of ROS within semen can be reduced by augmenting the scavenging capacity of seminal plasma using oral antioxidant supplementation. In fact, the benefits of oral antioxidant therapy has been described in numerous articles. By the way of reference, such articles include Comhaire et al, The Effects of Combined Conventional Treatment, Oral Antioxidants and Essential Fatty Acids on Sperm Biology in Subfertile Men, Prostaglandins Leuko Essent Fatty Acids, 63, 159-165 (2000); Lenzi et al, Placebo-Controlled, Double-blind, Cross-over Trial of Gluthathione therapy in male infertility, Hum Reprod, 8, 1657-1662 (1993); Greco et al, Reduction of the Incidence of Sperm DNA Fragmentation by Oral Antioxidant Treatment. J Androl, 17, 276-287 (2005); Tremellen et al, A Randomised Control Trial Examining the Effect of an Antioxidant (Menevit) on Pregnancy Outcome During IVF-ICSI Treatment, Australian and New Zealand Journal of Obstetrics and Gynecology 47, 216-221 (2007); and Agarwal et al, Oxidative stress, DNA Damage and Apoptosis in Male Infertility, a Clinical Approach, BJU Int, 95, 503-507 (2005), the teachings of which are incorporated herein in their entirety.
However, there is no product in the market today that has the instantly disclosed combination of antioxidants, minerals and vitamins. Moreover, the prior art does not teach the steps described herein to enhance the natural fertility process. At least one object of the present invention is to address such a need in the field.
Excessive concentration of ROS can cause extensive sperm DNA damage and membrane peroxidation. In general ROS includes reactive moieties such as hydroxyl radicals (OH−), ionic species such as superoxide anions (O2−), and neutral but highly reactive oxidizing molecules such hydrogen peroxides (H2O2). In semen, such species are predominantly generated by leukocytes or morphologically abnormal sperms. It has been described in the art that ROS plays both physiological and pathological roles in maturation of sperm cells. For example, at normal baseline ROS concentrations, sperms are properly matured as ROS modulates the regulation of the normal sperm function in various cascades including but not limited to sperm-oocyte fusion, acrosome reaction and sperm capacitation.
On the other hand, excess ROS concentrations result in direct insult on cellular components such as lipids, proteins and DNA, thus interfering with normal cell function. Traditional semen analysis methodologies fail to detect DNA damage caused by ROS. In fact, in many cases infertile men who undergo a clinical workup show normal sperm parameters, including sperm count motility and morphology. However, when compared with healthy fertile men, at least a subpopulation of these infertile men, show higher concentrations of oxidants in their seminal fluid which may be coupled with significantly lower concentrations of antioxidant as compared to healthy fertile men.
At the genomic level, excess concentrations of ROS modifies sperm DNA structure in a number of ways. For example, ROS can induce chromatin cross-linking, DNA base oxidation and cause high frequencies of single and double DNA strand breaks. Even though, sperms with damaged DNA may still fertilize the oocyte, the degree of DNA damage can have profound implications in normality of embryonic development resulting in higher miscarriage rates, birth defects or the long-term health of the progeny.
Current medical approach to facilitate embryonic development and pregnancy uses invasive techniques collectively referred to as Assisted Reproductive Techniques (“ART”), including Intrauterine Insemination (“IUI”), In vitro Fertilization (“IVF”) and Intracytoplasmic Sperm Injection (“ICSI”). However, such techniques generally have an average rate of success of about 30%. At least one explanation for such poor outcome is the fact that the semen and the sperm analysis techniques employed during ART cannot differentiate sperms with DNA damage from the normal ones.
Moreover, ART modes of fertilization have been linked with birth defects and incidences of childhood cancer, e.x. acute leukemia and lymphoma. Nevertheless, ART remains the only viable option for infertile couples. Another shortcoming of the ART is the cost. Couples on average undergo several IVF attempts to achieve a pregnancy, therefore undertaking huge expenses. Additionally, the risk of failure often causes intense emotional trauma.
Moreover, ART can not and does not address the damage done by ROS to sperm and ultimately to the fertilized egg. Therefore, there is a need in the art to address the impact of Sperm Oxidative Stress (“SOS”) among infertile couples. Currently, there are no effective and generally accepted pharmacotherapy that can combat the problem of male infertility associated with SOS. Thus, there is a need for convenient, inexpensive fertility methodologies and products to aid and improve couple's fertility potential. There is also a need for a kit that will provide couples in need with all products, tools and material required to facilitate a comprehensive plan for achieving a successful pregnancy.